In general, it is known that a polysaccharide (with hydrophilic character) appropriately functionalized with molecules having hydrophobic character can produce an assembling system with nanohydrogel characteristics if exposed to particular conditions in a water environment.
Nanohydrogels are acquiring considerable importance in pharmaceutical terms since they can be used as carrier compounds for drugs and be administered both in humans and animals by inhalation, parenterally (i.v, i.m, s.c.) or topically supported by an appropriate device and/or dispersant means.
Currently, different methods are known for the preparation of functionalized polysaccharides for the preparation of nanohydrogel, the most famous of which is derivatization of the polymer chains with derivatives of cholesterol or colanic acid. Said molecules appropriately bonded to the polysaccharide chains give the system the right amphiphilicity such as to allow the process of self-assembling in water and/or physiological solutions, after appropriate treatment of the compound.
A first of these treatments consists in subjecting the functionalized polysaccharide to sonication. The ultrasonic vibrations are able to induce the formation of small-dimension nanohydrogel. The ultrasounds generate in the polymer suspension micro-bubbles which, by imploding, give rise to the phenomenon of cavitation which promotes separation of the polymer chains favouring the formation of a nanoparticle suspension. Another method consists in solubilising the functionalized polysaccharide in an appropriate solvent and adding dropwise the solution obtained in water. In these conditions the system precipitates inducing the formation of nanoparticles. Yet another method consists in subjecting the functionalized polysaccharide to dialysis against water or water solution once said polysaccharide has been solubilised in an organic solvent. The slow inlet of water through the dialysis tubes causes the formation of small-dimension nanohydrogel by spontaneous self-assembling.
As mentioned above, one of the possible applications of nanohydrogels is in pharmaceutical preparations administered parenterally. The nanohydrogel can incorporate a pharmacologically active ingredient and function as a carrier for the administration thereof.
In this context, the capacity of the polymer derivative to give rise to nanohydrogel with satisfactory yield, the stability of said nanohydrogels in both conservation conditions and in water and physiological fluids, and the yield of the bioactive molecule loading process, in addition to the possibility of being sterilised for systemic administration without causing drug loss are essential requirements.
Currently the nanohydrogel systems present in the literature are unsuitable for industrial use also due to the low yields obtained after purification and the low degree of drug loading that can be obtained. Due to the high water content of the nanohydrogel systems, in fact, separation and concentration by means of ultracentrifugation is often insufficient or in any case produces low yields. The nature of the hydrophobic domains within the nanohydrogel, furthermore, is often inadequate for a high loading of drugs.
The need was therefore felt for a more effective polymer platform in terms of formation of nanohydrogel, in terms of loading of drugs and in terms of stability of the nanohydrogels formed in both physiological conditions and in conservation conditions.
The inventors of the present patent application have found an extremely versatile method of synthesis of amphiphilic derivatives of polysaccharides for the preparation of nanohydrogels responding to the above needs.